DESCRIPTION(adapted from applicant's abstract): Deafness resulting from destruction of the inner ear is accompanied by partial degeneration of the auditory nerve as well as anatomical, physiological and molecular changes throughout the central auditory nervous system. These changes vary considerably among deaf individuals. By hypothesis, these individual differences are associated with the large differences across subjects in psychophysical and speech recognition performance with cochlear implants. In the set of experiments proposed in this application, we will use neurophysiological measures to characterize the large psychophysical changes that occur following deafening and implantation of the cochlea. We will then examine the functional effects of post-deafening treatments, such as chronic electrical stimulation of the cochlea, that are intended to retard the long-term deleterious effects of deafness on the auditory system. The functional responses to electrical stimulation through cochlear implants will be assessed at the psychophysical level in humans and guinea pigs by measuring detection threshold functions and discrimination functions, and at the neurophysiological level in guinea pigs by measuring spatial and temporal responses of neurons in the inferior colliculus to electrical stimulation and by measuring gross potentials that reflect summed neural activity at peripheral (ECAP and EABR) and central (EMLR) sites along the auditory pathway. Three aims will be addressed. In Aim 1 we will compare psychophysical responses obtained from humans and guinea pigs to determine the relevance of guinea pig data to humans. In Aim 2 we will characterize the pronounced short-term effects of deafening and implantation procedures on the psychophysical and neurophysiological responses to electrical stimulation using the guinea-pig animal model. In Aim 3, we will test hypotheses about the functional benefits of post-deafening treatment of the ear. The results of these experiments will lead to better use of animal (guinea pig) models for auditory prosthesis experiments, they will provide a better understanding of the functional (diagnostic) implications of commonly used psychophysical measures such as detection threshold level, and they will have direct application to treatment protocols for deaf and severely hearing-impaired patients.